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Perspectives in Biology and Medicine 43.3 (2000) 406-448

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Infectious Causation of Disease: An Evolutionary Perspective **

Gregory M. Cochran, Paul W. Ewald, and Kyle D. Cochran *



Over the past two centuries, diseases have been separated into three categories: infectious diseases, genetic diseases, and diseases caused by too much or too little of some noninfectious environmental constituent. At the end of the 19th century, the most rapid development was in the first of these categories; within three decades after the first cause-effect linkage of a bacterium to a disease, most of the bacterial causes of common acute infectious diseases had been identified. This rapid progress can be attributed in large part to Koch's postulates, a rigorous systematic approach to identification of microbes as causes of disease. Koch's postulates were useful because they could generate conclusive evidence of infectious causation, particularly when (1) the causative organisms could be isolated and experimentally transmitted, and (2) symptoms occurred soon after the onset of infection in a high proportion of infected individuals. While guiding researchers down one path, however, the postulates directed them away from alternative paths: researchers attempting to document infectious causation were guided away from diseases that had little chance of fulfilling the postulates, even though they might have been infectious.

During the first half of the 20th century, when the study of infectious agents was shifting from bacteria to viruses, Mendel's genetics was being integrated into the study of disease. Some diseases could not be ascribed to infectious causes using Koch's postulates but could be shown to have [End Page 406] genetic bases, particularly if they were inherited according to Mendelian ratios. Mendelís genetics and Kochís postulates thus helped create a conceptual division of diseases into genetic and infectious categories, a division that persists today.

The third category--diseases resulting from noninfectious environmental causes--has a longer history. The known associations of poisons with illness provided a basis for understanding physical agents as causes of disease. The apparent "contagiousness" of some chemical agents, such as the irritant of poison ivy, led experts to consider that diseases could be contagious without being infectious. Even after the discovery of causative microbes during the last quarter of the 19th century, many infectious diseases were considered contagious through the action of poisons, but not necessarily infectious [1].

The difficulty of distinguishing noninfectious chemical insults from infection is often attributable to the similarities between the spread of diseases caused by a common source of toxins and the spread of infectious disease. Milk sickness, for example, resulted from the consumption of white snakeroot by milk cows and was widespread in the midwestern United States during the 19th century [2]. The spread of illness among those who drank contaminated milk could resemble the spread of infectious diseases, especially food-borne infectious diseases, and during the first quarter of the 20th century, there was disagreement over whether milk sickness was caused by infection or an environmental toxin [3]. Distinguishing microbes from environmental toxins as etiologic agents is still a source of controversy. The lytico-bodig of Guam, for example, which can resemble parkinsonism or amyotrophic lateral sclerosis, is attributed by some researchers to infection and by others to a toxin present in foods derived from cycads [4].

Diseases attributable to a paucity of an environmental constituent include scurvy (insufficient vitamin C), rickets (vitamin D), beriberi (vitamin B1), and goiter (iodine). After establishment of the germ theory, dietary deficiency diseases were sometimes mistakenly attributed to infection, but these uncertainties were generally resolved fairly rapidly through nutrient supplementation. During the first half of this century, for example, expert opinion was divided between infectious and dietary causation of pellagra, but by the middle of this century it was generally ascribed to niacin deficiency. Although the primary period of discovery of dietary deficiency diseases occurred prior to the middle of the 20th century, the recent association of folic acid deficiency with spina bifida demonstrates that some diseases may still be ascribed to dietary deficiency.

These three...